The spatial organization of transcriptional control

Nature Reviews Genetics, Journal Year: 2022, Volume and Issue: 24(1), P. 53 - 68

Published: Sept. 14, 2022

Language: Английский

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Liquid–Liquid Phase Separation in Chromatin

Cold Spring Harbor Perspectives in Biology, Journal Year: 2021, Volume and Issue: 14(2), P. a040683 - a040683

Published: June 14, 2021

Karsten Rippe Division of Chromatin Networks, German Cancer Research Center (DKFZ) and Bioquant, 69120 Heidelberg, Germany Correspondence: Karsten.Rippe{at}dkfz.de

Language: Английский

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Identifying synergistic high-order 3D chromatin conformations from genome-scale nanopore concatemer sequencing

Nature Biotechnology, Journal Year: 2022, Volume and Issue: 40(10), P. 1488 - 1499

Published: May 30, 2022

Language: Английский

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Analysis of sub-kilobase chromatin topology reveals nano-scale regulatory interactions with variable dependence on cohesin and CTCF

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: April 19, 2022

Abstract Enhancers and promoters predominantly interact within large-scale topologically associating domains (TADs), which are formed by loop extrusion mediated cohesin CTCF. However, it is unclear whether complex chromatin structures exist at sub-kilobase-scale to what extent fine-scale regulatory interactions depend on extrusion. To address these questions, we present an MNase-based chromosome conformation capture (3C) approach, has enabled us generate the most detailed local interaction data date (20 bp resolution) precisely investigate effects of CTCF depletion architecture. Our reveal that cis -regulatory elements have distinct internal nano-scale structures, insulation dependent CTCF, but independent cohesin. In contrast, find causes a subtle reduction in longer-range enhancer-promoter can cause rewiring contacts. Together, our show not essential for interactions, contributes their robustness specificity precise regulation gene expression.

Language: Английский

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The role of chromatin loop extrusion in antibody diversification

Nature reviews. Immunology, Journal Year: 2022, Volume and Issue: 22(9), P. 550 - 566

Published: Feb. 15, 2022

Language: Английский

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Enhancer–promoter interactions can bypass CTCF-mediated boundaries and contribute to phenotypic robustness

Nature Genetics, Journal Year: 2023, Volume and Issue: 55(2), P. 280 - 290

Published: Jan. 30, 2023

Language: Английский

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Chromatin accessibility: methods, mechanisms, and biological insights

Nucleus, Journal Year: 2022, Volume and Issue: 13(1), P. 238 - 278

Published: Nov. 20, 2022

Access to DNA is a prerequisite the execution of essential cellular processes that include transcription, replication, chromosomal segregation, and repair. How proteins regulate these function in context chromatin its dynamic architectures an intensive field study. Over past decade, genome-wide assays new imaging approaches have enabled greater understanding how access genome regulated by nucleosomes associated proteins. Additional mechanisms may control accessibility vivo compaction phase separation – are beginning be understood. Here, we review ongoing development measurements, summarize different molecular structural shape landscape, detail many important biological functions linked accessibility.

Language: Английский

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Loop stacking organizes genome folding from TADs to chromosomes

Molecular Cell, Journal Year: 2023, Volume and Issue: 83(9), P. 1377 - 1392.e6

Published: May 1, 2023

Language: Английский

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Direct observation of a condensate effect on super-enhancer controlled gene bursting

Cell, Journal Year: 2024, Volume and Issue: 187(2), P. 331 - 344.e17

Published: Jan. 1, 2024

Enhancers are distal DNA elements believed to loop and contact promoters control gene expression. Recently, we found diffraction-sized transcriptional condensates at genes controlled by clusters of enhancers (super-enhancers). However, a direct function endogenous in controlling expression remains elusive. Here, develop live-cell super-resolution multi-color 3D-imaging approaches investigate putative roles the regulation super-enhancer Sox2. In contrast enhancer distance, find instead that condensate's positional dynamics better predictor A basal bursting occurs when condensate is far (>1 μm), but burst size frequency enhanced moves proximity (<1 μm). Perturbations cohesin local do not prevent affect its enhancement. We propose three-way kissing model whereby interacts transiently with locus regulatory bursting.

Language: Английский

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The Mediator complex regulates enhancer-promoter interactions

Nature Structural & Molecular Biology, Journal Year: 2023, Volume and Issue: 30(7), P. 991 - 1000

Published: July 1, 2023

Abstract Enhancer-mediated gene activation generally requires physical proximity between enhancers and their target promoters. However, the molecular mechanisms by which interactions promoters are formed not well understood. Here, we investigate function of Mediator complex in regulation enhancer-promoter interactions, combining rapid protein depletion high-resolution MNase-based chromosome conformation capture approaches. We show that leads to reduced interaction frequencies, associated with a strong decrease expression. In addition, find increased CTCF-binding sites upon depletion. These changes chromatin architecture redistribution Cohesin on reduction occupancy at enhancers. Together, our results indicate complexes contribute provide insights into communication is regulated.

Language: Английский

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